Refractory Shock Research Articles

An analysis of reported cases of hemophagocytic lymphohistiocytosis (HLH) after COVID-19 vaccination

ABSTRACT Although COVID-19 vaccines are an effective public health tool to combat the global pandemic, serious adverse events, such as hemophagocytic lymphohistiocytosis (HLH), caused by them are a concern. In this systematic review, cases of HLH reported after COVID-19 vaccination have been examined to understand the relationship between the two and propose effective therapeutic strategies. Furthermore, ruxolitinib’s potential as a cytokine inhibitor and its affinity for CD25 were initially assessed through molecular docking, aiming to aid targeted HLH therapy. PubMed and Web of Science databases were searched for published individual case reports on the occurrence of HLH after the administration of any COVID-19 vaccine. A total of 17 articles (25 patients) were included in this qualitative analysis. Furthermore, molecular docking was employed to investigate the therapeutic potential of ruxolitinib for HLH after COVID-19 vaccination. The mean age of patients who developed HLH after COVID-19 vaccination was 48.1 years. Most HLH episodes occurred after the BNT162b2 mRNA COVID-19 vaccination (14/25 cases) and to an extent after the ChAdOx1 nCov‐19 vaccination (5/25 cases). Almost all affected patients received steroid and antibiotic therapy. Three patients died despite treatment because of esophagus rupture, neutropenic fever, bacteroides bacteremia, refractory shock, and encephalopathy and shock. Visual docking results of IL-2 Rα and ruxolitinib using the Discovery Studio 2019 Client software yielded a model score of 119.879. The findings highlight the importance of considering and identifying the adverse effects of vaccination and the possibility of using ruxolitinib for treating HLH after COVID-19 vaccination.

Removal of obstructive organized tracheo-bronchial clots under respiratory support using veno-venous extracorporeal membrane oxygenation in a patient with blunt thoracic trauma: a case report

BackgroundIt has been reported that veno-venous extracorporeal membrane oxygenation is useful for treating patients with acute respiratory failure following severe thoracic trauma. However, the removal of an obstructive organized tracheo-bronchial clot under respiratory support using extracorporeal membrane oxygenation in a patient with trauma has never been reported.Case presentationA teenage female was injured in a fall and experienced right open hemopneumothorax and bilateral lung contusions. Since she was in refractory shock due to bleeding into the right thoracic cavity, we performed right thoracotomy and resection of the lacerated right middle lobe. After hemorrhage control, her respiratory status could not be maintained under mechanical respiratory support. Therefore, we initiated veno-venous extracorporeal membrane oxygenation. Although her respiratory failure gradually improved, the removal of obstructing tracheo-bronchial organized blood clots using bronchoscopy was required daily. Because of the size and firm adherence of organized clots to the airway membrane, we performed a tracheostomy to remove organized clots directly through the incision under extracorporeal membrane oxygenation without any adverse events on day 9. The next day, she was successfully removed from extracorporeal membrane oxygenation.ConclusionsExtracorporeal membrane oxygenation could provide respiratory support not only for acute respiratory failure but also for removal of obstructing tracheo-bronchial organized clots in patients with severe lung injury following trauma.

The Vasopressin Loading for Refractory septic shock (VALOR) study: a prospective observational study

BackgroundVasopressin is a second-line vasoactive agent for refractory septic shock. Vasopressin loading is not generally performed because of the lack of evidence for its effects and safety. However, based on our previous findings, we hypothesized it can predict the responsibility to vasopressin infusion with safety, and prospectively examined it in the present study.MethodsVasopressin loading was performed via the intravenous administration of a bolus of 1 U, followed by its continuous infusion at 1U/h in patients with septic shock treated with ≥ 0.2 μg/kg/min noradrenaline. An arterial pressure wave analysis was conducted, and endocrinological tests were performed immediately prior to vasopressin loading. We classified patients into responders/non-responders based on mean arterial pressure (MAP) changes after vasopressin loading. Based on our previous findings, the lower tertile of MAP changes was selected as the cut-off. The change in the catecholamine index (CAI) after 6 h was assigned as the primary outcome. Digital ischemia, mesenteric ischemia, and myocardial ischemia during the admission period were prospectively and systematically recorded as adverse events.ResultsNinety-two patients were registered during the study period and examined. Sixty-two patients with a MAP change > 22 mmHg were assigned as responders and the others as non-responders. Blood adrenocorticotropic hormone levels were significantly higher in non-responders. Stroke volume variations were higher in responders before loading, while stroke volume and dP/dtmax were higher in responders after loading. Median CAI changes were − 10 in responders and 0 in non-responders, which was significantly lower in the former (p < 0.0001). AUROC of MAP change with vasopressin loading to predict CAI change < 0 after continuous infusion was 0.843 with sensitivity of 0.92 and specificity of 0.77. Ischemia events were observed in 5 cases (5.4%).ConclusionsVasopressin loading may be safely introduced for septic shock. Vasopressin loading may be used to predict responses to its continuous infusion and select appropriate strategies to increase blood pressure.

Hemodynamic management of septic shock: beyond the Surviving Sepsis Campaign guidelines.

Although the Surviving Sepsis Campaign guidelines provide standardized and generalized guidance, they are less individualized. This review focuses on recent updates in the hemodynamic management of septic shock. Monitoring and intervention for septic shock should be personalized according to the phase of shock. In the salvage phase, fluid resuscitation and vasopressors should be given to provide life-saving tissue perfusion. During the optimization phase, tissue perfusion should be optimized. In the stabilization and de-escalation phases, minimal fluid infusion and safe fluid removal should be performed, respectively, while preserving organ perfusion. There is controversy surrounding the use of restrictive versus liberal fluid strategies after initial resuscitation. Fluid administration after initial resuscitation should depend upon the patient's fluid responsiveness and requires individualized management. A number of dynamic tests have been proposed to monitor fluid responsiveness, which can help clinicians decide whether to give fluid or not. The optimal timing for the initiation of vasopressor agents is unknown. Recent data suggest that early vasopressor initiation should be considered. Inotropes can be considered in patients with decreased cardiac contractility associated with impaired tissue perfusion despite adequate volume status and arterial blood pressure. Venoarterial extracorporeal membrane oxygenation should be considered for refractory septic shock with severe cardiac systolic dysfunction.

The Eight Unanswered and Answered Questions about the Use of Vasopressors in Septic Shock.

Septic shock is mainly characterized-in addition to hypovolemia-by vasoplegia as a consequence of a release of inflammatory mediators. Systemic vasodilatation due to depressed vascular tone results in arterial hypotension, which induces or worsens organ hypoperfusion. Accordingly, vasopressor therapy is mandatory to correct hypotension and to reverse organ perfusion due to hypotension. Currently, two vasopressors are recommended to be used, norepinephrine and vasopressin. Norepinephrine, an α1-agonist agent, is the first-line vasopressor. Vasopressin is suggested to be added to norepinephrine in cases of inadequate mean arterial pressure instead of escalating the doses of norepinephrine. However, some questions about the bedside use of these vasopressors remain. Some of these questions have been well answered, some of them not clearly addressed, and some others not yet answered. Regarding norepinephrine, we firstly reviewed the arguments in favor of the choice of norepinephrine as a first-line vasopressor. Secondly, we detailed the arguments found in the recent literature in favor of an early introduction of norepinephrine. Thirdly, we reviewed the literature referring to the issue of titrating the doses of norepinephrine using an individualized resuscitation target, and finally, we addressed the issue of escalation of doses in case of refractory shock, a remaining unanswered question. For vasopressin, we reviewed the rationale for adding vasopressin to norepinephrine. Then, we discussed the optimal time for vasopressin administration. Subsequently, we addressed the issue of the optimal vasopressin dose, and finally we discussed the best strategy to wean these two vasopressors when combined.

Melioidosis presenting with multiple liver abscesses

Abstract A 48-year-old male patient presented with a history of fever, abdominal pain and cough for the preceding 14 days. Abdominal examination revealed tenderness in the right hypochondrium. Radiological features were suggestive of multiple liver abscesses. Ultrasonography-guided percutaneous catheter insertion into the largest measuring abscess was done. Pus culture grew Burkholderia pseudomallei spp. The patient was started on intravenous meropenem initially which was changed to IV cefoperazone-sulbactam as per the sensitivity pattern. The patient died on the 16th day of admission due to refractory septic shock. The present case highlights the fact that melioidosis is emerging as an important cause and should be considered in the differential diagnosis in patients presenting with multiple liver abscesses and systemic sepsis.

Clinical Use of CathPCI Registry Risk Score and Its Validation to Predict Long-Term Mortality

Risk models to estimate percutaneous coronary intervention (PCI) mortality have limited value in complex high-risk patients. However, it was improved by a recently developed bedside model to predict in-hospital mortality using data from the American College of Cardiology CathPCI Registry that included 706,263 patients. The median risk-standardized in-hospital mortality rate was 1.9%. In an attempt to validate this model in patients admitted because of acute coronary ischemia to predict in-hospital, 30-day, and 1-year mortality, we applied the proposed risk score to the study population of the Acute Coronary Syndrome Israeli Survey (ACSIS). This study was conducted for 2 months in 2018 and included all patients admitted to 25 coronary care units and cardiology departments in Israel. The ACSIS included 1,155 patients admitted because of acute myocardial infarction and who underwent PCI. In-hospital, 30-day, and 1-year mortality were 2.3%, 3.1%, and 6.2%, respectively. The CathPCI risk score yielded an area under the receiver operating characteristic curve of 0.96 (95% confidence interval [CI] 0.94 to 0.99) for in-hospital mortality; 0.96 (95% CI 0.94 to 0.98) for the 30-day mortality, and 0.88 (95% CI 0.83 to 0.93) for the 1-year mortality. The current model also included frail patients, and those with aortic stenosis, refractory shock, and after cardiac arrest. In conclusion, the CathPCI Registry risk score was validated using data from the ACSIS. Because the ACSIS population comprised patients with acute ischemia including those with high-risk features this model demonstrates a wider scope of application compared with previous ones. In addition, the model seems to be suitable to predict also the 30-day and 1-year mortality.

Emergency surgical intervention in acute corrosive ingestion: single-center experience from India.

Surgical intervention for acute corrosive injury is often required. It is associated with considerable morbidity and mortality. Sparce data is available on the types and timing of surgery after acute corrosive ingestion and complications associated with the same. This is a retrospective single-center study from a tertiary care center in India. All patients who underwent surgical exploration after acute corrosive intake between January 2003 and June 2014 were enrolled in the study. Data on patients' presentation, their endoscopic findings, indications of surgery, type of surgery and post-operative follow-up was retrieved. Out of 170 patients who presented with acute corrosive ingestion, 24 patients (14.11%) required emergency surgery. The mean interval between ingestion and surgery was 9.92 ± 9.03 days. Presence of peritonitis was the most common indication for surgery (n = 10; 41.7%) followed by mediastinitis (n = 7; 29.2%). A total of 17 resectional and 7 non-resectional procedures were performed. Thirteen (54%) patients succumbed to their illness post-operatively due to multi-organ failure (n = 9), refractory shock (n = 3) or pulmonary thromboembolism (n = 1). Patients with early surgery (≤7 days) after corrosive ingestion had similar mortality compared to patients with late surgery (>7 days) (50% versus 67%; P = 0.30). Of the 11 surviving patients, eight patients (72%) underwent successful reconstructive surgery on follow-up. Emergency surgery after corrosive ingestion carries high morbidity and mortality. However, after the initial stormy acute phase, majority of patients can undergo successful reconstructive surgery on follow-up.

A Rare Cause of Refractory Vasodilatory Shock Due to Calcium Channel Blocker Toxicity from Drug-Drug Interaction Between Ritonavir-Boosted Nirmatrelvir (Paxlovid) And Manidipine

Herein, is a reported case of an 86-year-old woman, admitted due to complete atrioventricular block. During admission, she was diagnosed and treated with ritonavir-boosted nirmatrelvir (Paxlovid) for the coronavirus disease 2019 (COVID-19). Four days after initiating the treatment for COVID-19, an oral dose of 20 mg manidipine was administrated. Five hours later, the patient developed hypotension that eventually progressed to refractory shock requiring a maximum dose of 1.82 µg/kg/min of norepinephrine equivalent. Shock reversal dramatically improved within 17 hours after the cause of shock was diagnosed, and her having receiving specific treatment via intravenous calcium administration and high-dose insulin euglycemia therapy (HIE).

Clinical application of plasma exchange combined with continuous veno-venous hemofiltration dialysis in children with refractory Kawasaki disease shock syndrome

To study the role of plasma exchange combined with continuous blood purification in the treatment of refractory Kawasaki disease shock syndrome (KDSS). A total of 35 children with KDSS who were hospitalized in the Department of Pediatric Intensive Care Unit, Hunan Children's Hospital, from January 2019 to August 2022 were included as subjects. According to whether plasma exchange combined with continuous veno-venous hemofiltration dialysis was performed, they were divided into a purification group with 12 patients and a conventional group with 23 patients. The two groups were compared in terms of clinical data, laboratory markers, and prognosis. Compared with the conventional group, the purification group had significantly shorter time to recovery from shock and length of hospital stay in the pediatric intensive care unit, as well as a significantly lower number of organs involved during the course of the disease (P<0.05). After treatment, the purification group had significant reductions in the levels of interleukin-6, tumor necrosis factor-α, heparin-binding protein, and brain natriuretic peptide (P<0.05), while the conventional group had significant increases in these indices after treatment (P<0.05). After treatment, the children in the purification group tended to have reductions in stroke volume variation, thoracic fluid content, and systemic vascular resistance and an increase in cardiac output over the time of treatment. Plasma exchange combined with continuous veno-venous hemofiltration dialysis for the treatment of KDSS can alleviate inflammation, maintain fluid balance inside and outside blood vessels, and shorten the course of disease, the duration of shock and the length of hospital stay in the pediatric intensive care unit.

Cytokine Storm Syndrome Triggered by Extracorporeal Membrane Oxygenation in Pediatric Patients.

Cytokine storm syndrome (CSS) is a serious and potentially life-threatening condition caused by severe systemic inflammation, immune activation, and a positive feedback loop of cytokine release. Typically triggered by systemic infection, malignancy, monogenic or rheumatic disease, similar patterns of hyper-inflammation have been seen in patients undergoing cardiopulmonary bypass (CPB) and in patients treated with extracorporeal membrane oxygenation (ECMO). Typical treatments used for the prevention and treatment of CPB/ECMO-induced hyper-inflammation have not been shown to be substantially effective. Two patients suffering from ECMO-related CSS were identified by their severe hyper-inflammatory profile and life-threatening sequelae of vasodilatory shock and respiratory failure. Anakinra, an interleukin-1 receptor antagonist, was employed as specific cytokine-directed therapy for the treatment of CSS in these two patients to good effect, with significant improvement in hyper-inflammation and cardiorespiratory status. The use of cytokine-directed therapies in CPB/ECMO-related CSS has great potential to improve the treatment and outcomes of this serious condition.

Application of veno-arterio-venous extracorporeal membrane oxygenation in patients with critical respiratory failure combined with refractory shock

Objective: To preliminarily analyze the application experience of veno-arterio-venous extracorporeal membrane oxygenation (VAV-ECMO).The VAV-ECMO is a rescue strategy for patients with extremely critical respiratory failure combined with refractory shock. Methods: From February 2016 to February 2022, the characteristics and outcomes of patients who were started on either veno-venous or veno-arterial ECMO due to respiratory or hemodynamic failure, and then converted to VAV-ECMO in respiratory intensive care unit (ICU) of Beijing Chaoyang Hospital were analyzed. Results: A total of 15 patients underwent VAV-ECMO, aged 53 (40, 65) years, and 11 of whom were male. Within the group, VV-ECMO was initially used in 12 patients due to respiratory failure, but then VAV-ECMO was used due to cardiogenic shock (7/12) and septic shock (4/12), while VAV-ECMO was established in two patients due to lung transplantation. One patient was diagnosed with pneumonia complicated by septic shock, which was initially determined to be VA-ECMO, but then switched to VAV-ECMO because it was difficult to maintain oxygenation. The time from the establishment of VV or VA-ECMO to the switch to VAV-ECMO was 3 (1, 5) days and the VAV-ECMO support time was 5 (2, 8) days. ECMO-related complications were bleeding, mostly in the digestive tract (n=4) and airway hemorrhage (n=4), without intracranial hemorrhage, and poor arterial perfusion of the lower limbs (n=2). Among these 15 patients, the overall ICU mortality was 53.3%. The mortality of patients who received VAV-ECMO due to septic shock and cardiogenic shock was 100% (4/4) and 42.8% (3/7), respectively. Two patients who received VAV-ECMO due to lung transplantation all survived. Conclusion: VAV-ECMO may be a safe and effective treatment for carefully selected patients with critical respiratory failure associated with cardiogenic shock or end-stage lung disease lung transplantation transition, however, patients with septic shock may benefit the least.

Increasing angiotensin-converting enzyme concentrations and absent angiotensin-converting enzyme activity are associated with adverse kidney outcomes in pediatric septic shock

BackgroundSepsis-induced endothelial dysfunction is proposed to cause angiotensin-converting enzyme (ACE) dysfunction and renin–angiotensin–aldosterone system (RAAS) derangement, exacerbating vasodilatory shock and acute kidney injury (AKI). Few studies test this hypothesis directly, including none in children. We measured serum ACE concentrations and activity, and assessed their association with adverse kidney outcomes in pediatric septic shock.MethodsA pilot study of 72 subjects aged 1 week–18 years from an existing multicenter, observational study. Serum ACE concentrations and activity were measured on Day 1; renin + prorenin concentrations were available from a previous study. The associations between individual RAAS components and a composite outcome (Day 1–7 severe persistent AKI, kidney replacement therapy use, or mortality) were assessed.Results50/72 subjects (69%) had undetectable ACE activity (< 2.41 U/L) on Day 1 and 27/72 (38%) developed the composite outcome. Subjects with undetectable ACE activity had higher Day 1 renin + prorenin compared to those with activity (4533 vs. 2227 pg/ml, p = 0.017); ACE concentrations were no different between groups. Children with the composite outcome more commonly had undetectable ACE activity (85% vs. 65%, p = 0.025), and had higher Day 1 renin + prorenin (16,774 pg/ml vs. 3037 pg/ml, p < 0.001) and ACE concentrations (149 vs. 96 pg/ml, p = 0.019). On multivariable regression, increasing ACE concentrations (aOR 1.01, 95%CI 1.002–1.03, p = 0.015) and undetectable ACE activity (aOR 6.6, 95%CI 1.2–36.1, p = 0.031) retained associations with the composite outcome.ConclusionsACE activity is diminished in pediatric septic shock, appears uncoupled from ACE concentrations, and is associated with adverse kidney outcomes. Further study is needed to validate these findings in larger cohorts.

Factors associated with circulatory death after out-of-hospital cardiac arrest: a population-based cluster analysis

BackgroundOut-of-hospital cardiac arrest (OHCA) is a common cause of death. Early circulatory failure is the most common reason for death within the first 48 h. This study in intensive care unit (ICU) patients with OHCA was designed to identify and characterize clusters based on clinical features and to determine the frequency of death from refractory postresuscitation shock (RPRS) in each cluster.MethodsWe retrospectively identified adults admitted alive to ICUs after OHCA in 2011–2018 and recorded in a prospective registry for the Paris region (France). We identified patient clusters by performing an unsupervised hierarchical cluster analysis (without mode of death among the variables) based on Utstein clinical and laboratory variables. For each cluster, we estimated the hazard ratio (HRs) for RPRS.ResultsOf the 4445 included patients, 1468 (33%) were discharged alive from the ICU and 2977 (67%) died in the ICU. We identified four clusters: initial shockable rhythm with short low-flow time (cluster 1), initial non-shockable rhythm with usual absence of ST-segment elevation (cluster 2), initial non-shockable rhythm with long no-flow time (cluster 3), and long low-flow time with high epinephrine dose (cluster 4). RPRS was significantly associated with this last cluster (HR, 5.51; 95% confidence interval 4.51–6.74).ConclusionsWe identified patient clusters based on Utstein criteria, and one cluster was strongly associated with RPRS. This result may help to make decisions about using specific treatments after OHCA.

A Review Evaluating Intravascular Access for High Volume Resuscitation: Can You Keep Up?

Anesthetists and anesthesiologists are frequently in the unique position of administering high-volume resuscitation in the setting of hemorrhage, hypovolemia, or vasodilatory shock. The ability to rapidly infuse intravenous (IV) fluid solutions differs vastly for different types and sizes of IV access. In patients that may require rapid large volume resuscitation, it is critical to understand the capacity of existing IV devices. Selecting the most appropriate IV access for patients can be paramount in preventing hypotension, end organ dysfunction, and even death. This article objectively reviews and compares the flow rates of commonly used central and peripheral intravenous devices to demonstrate the influence of catheter length and radius.

CLINICOETIOLOGICAL PROFILE, MANAGEMENT AND OUTCOME OF NEONATAL SHOCK PRESENTING WITHIN FIRST 72 HOURS OF LIFE

Objective: To study the ethology, presentation, response to treatment and outcome of neonatal shock which is one of the most common causes of morbidity and mortality in neonates while at the same time being amongst the less studied topics in pediatrics, with data from children and adult being extrapolated to the neonates. Study Design: This was a cross sectional observational study done in a government hospital of north India from 1 January 2023 to 30 April 2023.All the neonates aged 0 – 72 hours who presented to the neonatal intensive care unit (NICU) of the pediatric department of the hospital as a case of shock were included in the study. Shock was defined as decreased perfusion, altered mental status, diminished or bounding pulses, cool extremities or decreased urine output. Results: Our study included 71 patients (54.9% males and 45.1% females) out of which 77.5 % participants presented within 24 hours of birth. 54.9% babies had normal weight and 47.9% were early term. Babies born via LSCS were more likely to develop and present earlier with shock. 43.7% cases were attributed to respiratory distress syndrome, 32.4% cases to perinatal asphyxia and 27.1% to sepsis. Sepsis and Meconium aspiration were more likely to present earlier. 25.4% required triple inotropic support and 7% had catecholamine refractory shock. Mortality was 18.3% with maximum mortality seen in patients on triple inotropic support, all of whom presented with shock at less than 24 hours of age.

The Role of Blood Purification by HA330 as Adjunctive Treatment in Children with Septic Shock

Introduction: Despite advances in supportive care for critically ill patients, sepsis remains an important cause of death worldwide in the PICU. One of the hallmarks of sepsis is hyperinflammation due to the excessive release of inflammatory mediators. Recently, new therapeutic approaches, such as immune modulation and blood purification, have been tried to improve outcomes in patients with septic shock. Methods: This study is a prospective observational study composed of children with septic shock and the PELOD-2 score ≥10 or the PRISM-3 score ≥15. All received 2–4 h of HA330 treatment on 2 consecutive days, used as adjunctive therapy. The effectiveness of HA330 hemoperfusion was evaluated by improving the PELOD-2 and PRISM-3 scores, the vasoactive inotropic score (VIS), and inflammatory markers from baseline to 72 h after the use of HA330 hemoperfusion. Results: Twelve patients hospitalized in the PICU and diagnosed with septic shock between July 2021 and May 2022 were included in this study and received hemoperfusion with HA330. The average PELOD-2 and PRISM-3 scores decreased significantly from 9.5 (IQR: 6.5–13.0) at baseline to 2.0 (IQR: 0–6.5) at 72 h (p = 0.002) and from 16.5 (IQR: 15.0–20.5) at baseline to 5.5 (IQR: 2.0–9.5) at 72 h (p = 0.002), respectively. The VIS decreased significantly from baseline to 72 h (p = 0.003). IL-6, procalcitonin, and lactate levels also decreased significantly from baseline to 72 h (p = 0.005, 0.03, and 0.03, respectively). Two of 12 patients expired due to their underlying condition (2/12, 16.7%). Device-related adverse events did not occur in this study. Conclusions: Our observational case series suggests a possible role for HA330 hemoperfusion as an adjunctive treatment of refractory septic shock in children with high severity scores in the context of rapid improvement in organ dysfunction, without serious adverse effects.

Critical Illness-Related Corticosteroid Insufficiency (CIRCI) Among Patients with COVID-19 at a Tertiary Hospital: Clinical Characteristics and Outcomes.

Among critically ill patients, there is usually impairment of the hypothalamic-pituitary-adrenal axis, leading to a condition known as critical illness-related corticosteroid insufficiency (CIRCI). This investigation aims to determine the incidence of and characterize CIRCI among patients with COVID-19 as well as to analyze the outcomes of these critically ill patients. This is a single-center, retrospective cohort study that investigated the occurrence of CIRCI among critically ill patients infected with COVID-19. In this cohort, there were 145 COVID-19-positive patients with refractory shock, which reflects that 22.94% of the COVID-19 admissions have probable CIRCI.Patients who were given corticosteroids were found to have statistically significant longer median days on a ventilator (p=0.001). However, those on the corticosteroid arm were at higher risk of morbidity and mortality and a greater proportion had organ dysfunction. Multivariable logistic regression analysis revealed that SOFA score was a significant predictor of mortality in CIRCI (p=0.013). CIRCI has a unique presentation among patients with COVID-19 because of the presence of a high level of inflammation in this life-threatening infection. It is possibly a harbinger of a markedly increased risk of mortality in these patients.

The Immunoadsorption Effect of Veno-arterial Extracorporeal Membrane Oxygenation in Refractory Septic Shock, Ventilator-associated Pneumonia, and Acute Respiratory Distress Syndrome Following Severe Pulmonary Contusions

Background: The utilization of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) for immunoadsorption has proven efficacious in reducing mortality rates among neonatal and pediatric patients afflicted with severe sepsis and septic shock. However, the effectiveness of this treatment in adult patients with septic shock remains controversial. Objective: This study was designed to assess the potential of VA-ECMO as an immunoadsorption therapy in patients with severe sepsis and septic shock. The primary objective of this study is to evaluate the efficacy of VA-ECMO in improving clinical outcomes, including acute respiratory distress syndrome (ARDS) and ventilator-associated pneumonia (VAP), weaning from mechanical ventilation, the length of intensive care unit (ICU) stay, and mortality rates in patients with concurrent severe pulmonary contusions, septic shock, and respiratory failure resulting from ARDS and VAP. Methods: This study enrolled a cohort of 100 adult patients with severe pulmonary contusions resulting in persistent respiratory failure despite ten days of mechanical ventilation. These patients subsequently developed severe sepsis, VAP with ARDS presentation, and high Murray score (&gt;3 points), Sequential Organ Failure Assessment (SOFA) score (&gt; 12 points), and Clinical Pulmonary Infection Score (CPIS) (&gt; 6 points). The patients were then divided into two groups: group A (n = 50) received conventional management, while group B (n = 50) underwent VA-ECMO. Moreover, the outcomes, including improvement in ARDS and VAP, successful weaning from mechanical ventilation, length of ICU stay, improvement of one or all parameters of Murray, SOFA, and CPIS scores, morbidity rate, and mortality rate were compared between the two groups and recorded after 14 days of treatment. Results: This study revealed that patients in group B showed significant improvement in Murray, SOFA, and CPIS scores. Furthermore, a large percentage of patients in group B were successfully weaned from both inotropic support and mechanical ventilation and were discharged from ICU. However, no significant difference in the mortality rate was observed between the two groups. Conclusion: VA-ECMO notably impedes the progression of sepsis, shortens ICU stay, and expedites the weaning from inotropic support and mechanical ventilation. However, it has no impact on the mortality rate of adult patients with septic shock.

Initiating angiotensin II at lower vasopressor doses in vasodilatory shock: an exploratory post-hoc analysis of the ATHOS-3 clinical trial

BackgroundHigh dose vasopressors portend poor outcome in vasodilatory shock. We aimed to evaluate the impact of baseline vasopressor dose on outcomes in patients treated with angiotensin II (AT II).MethodsExploratory post-hoc analysis of the Angiotensin II for the Treatment of High-Output Shock (ATHOS-3) trial data. The ATHOS-3 trial randomized 321 patients with vasodilatory shock, who remained hypotensive (mean arterial pressure of 55–70 mmHg) despite receiving standard of care vasopressor support at a norepinephrine-equivalent dose (NED) > 0.2 µg/kg/min, to receive AT II or placebo, both in addition to standard of care vasopressors. Patients were grouped into low (≤ 0.25 µg/kg/min; n = 104) or high (> 0.25 µg/kg/min; n = 217) NED at the time of study drug initiation. The primary outcome was the difference in 28-day survival between the AT II and placebo subgroups in those with a baseline NED ≤ 0.25 µg/kg/min at the time of study drug initiation.ResultsOf 321 patients, the median baseline NED in the low-NED subgroup was similar in the AT II (n = 56) and placebo (n = 48) groups (median of each arm 0.21 µg/kg/min, p = 0.45). In the high-NED subgroup, the median baseline NEDs were also similar (0.47 µg/kg/min AT II group, n = 107 vs. 0.45 µg/kg/min placebo group, n = 110, p = 0.75). After adjusting for severity of illness, those randomized to AT II in the low-NED subgroup were half as likely to die at 28-days compared to placebo (HR 0.509; 95% CI 0.274–0.945, p = 0.03). No differences in 28-day survival between AT II and placebo groups were found in the high-NED subgroup (HR 0.933; 95% CI 0.644–1.350, p = 0.71). Serious adverse events were less frequent in the low-NED AT II subgroup compared to the placebo low-NED subgroup, though differences were not statistically significant, and were comparable in the high-NED subgroups.ConclusionsThis exploratory post-hoc analysis of phase 3 clinical trial data suggests a potential benefit of AT II introduction at lower doses of other vasopressor agents. These data may inform design of a prospective trial.Trial registration: The ATHOS-3 trial was registered in the clinicaltrials.gov repository (no. NCT02338843). Registered 14 January 2015.